Yield Fixation and Evaluation at Different Processing Stages

Standard Operating Procedure (SOP) for the Calculation of  Yield and finalize the Limit at the different stages of drug product processing/manufacturing. This SOP is also applicable for Investigation of out of limit yield obtained during processing.

Calculation of  Yield and finalize the Limit

1.0   OBJECTIVE :

    • To lay down a procedure for fixation of yield and investigation of out of limits yield obtained at various stages of processing of a product.

2.0   SCOPE :

    • This SOP shall be applicable for all Batch Records (Batch Manufacturing Record and Batch Packaging Record) for Calculation of  Yield and finalize the Limit at the different processing stages.
    • This SOP is also applicable for Investigation of out of limit yield obtained at pharmaceutical drug manufacturing plants.

3.0   RESPONSIBILITY- YIELD CALCULATION :

    • Officer/ Executive Production: Evaluation of yields and Investigation of out of limit.
    • Officer / Executive QA: Review of calculation data and Investigation of out of limit obtained.
    • Head production: Review of Investigation of out of limit result obtained.
    • Head, Q A: Compliance to SOP
    • DEFINITION (S)
    • Yield is a rationale of usable quantity obtained from a process to the actual starting quantity provided.

4.0   PROCEDURE FOR CALCULATION OF YIELD :

    • % Yield (henceforth referred to as Yield) shall be evaluated at each stage were the quantifiable measure of a product is possible.
    • However, yield shall be evaluated at different stages mentioned below but not limited to, depending on the nature of the process,
      • End of granulation stage/ Dry Mixing
      • Sizing / Compaction and Milling
      • End of Blending
      • Completion of compression/ filling
      • End of coating*
      • End of packing
    • * Yield to be evaluated at each coating process for products where coating to be done in multiple stages (e.g. Seal coating, Polymer coating, Enteric coating, Polishing, Etc.)
    • Two types of yields shall be evaluated: % actual yield and reconciliation yield.

Yield Calculation Formula

    • The reconciliation shall be done for each stage.
    • While undertaking reconciliation, Loss during the process, rejection, samples, and actual quantity shall be evaluated.
Stage Parameter UOM
A Actual batch size of the preceding stage Kg
B Actual weight of the stage Kg
C Samples for Analysis (QC + Inprocess) Kg
D Rejects Kg
E Loss during process Kg
    • Reconciliation Yield = (B+C+D+E)/A x 100 =………….%
    • When the packing of a product is done in multiple packs, the complete batch reconciliation shall be done after the completion of the last pack.
    • For the New Product :

    • For a new product, the yield limit at each individual stage shall be provided as a tentative limit.
    • If it is observed below tentative limits justification/ reasons to be provided in the concerned Batch Record.
    • This is also applicable for existing / validated products when a major change in the manufacturing process is introduced.
    • Assigning/ Resetting of limits shall be based on general process knowledge, batch size, sampling due to validation, etc.
    • If any unwarranted low yield values are observed as that of tentative limits, adequate investigation to be done,
    • However, the need of investigation depends on the nature of the process and decisions taken by stakeholders.
    • Tentative limits shall be as per Table 1.
    • However, limits may be made stringent or loose based on product nature / atypical process/ batch size/ packing types.

Table-1

For Tablets & Capsules (Up to 250,000 units)

Granulation/ Dry mixing Not Less than 99.0 %
Sizing/ Compaction & Milling Not Less than 98.5 %
Blending stage            Not Less than 98.0 %
Compression stage     Not Less than 97.5 %
Coating stage  Not Less than 97.0 %
Filling Stage Not Less than 96.5 %
Inspection stage          Not Less than 96.0 %
Packing stage Not Less than 95.5 %

For Tablets & Capsules (> 250,000 units)

Granulation/ Dry mixing Not Less than 99.5 %
Sizing/ Compaction & Milling Not Less than 99.0 %
Blending stage            Not Less than 98.5 %
Compression stage     Not Less than 98.0 %
Coating stage  Not Less than 97.5 %
Filling Stage Not Less than 97.0 %
Inspection stage          Not Less than 96.5 %
Packing stage Not Less than 96.0 %

Dry Powder injections

Blending Not Less than 99.0 %
Filling              Not Less than 98.0 %
Packing          Not Less than 97.0 %

Oral Dry Powder Suspension

Granulation/ Dry mixing Not Less than 99.0 %
Sizing/ Compaction & Milling Not Less than 98.5 %
Blending stage            Not Less than 98.0 %
Filling Stage Not Less than 97.5 %
Packing stage Not Less than 97.0 %
    • The yield for a product shall be fixed after completion of 10 manufacturing batches (excluding the validation batches) or at the time of completion of Product Quality Review (Refer SOP for APQR/PQR), whichever is early.
    • In case it is fixed after completion of 10 batches, a certificate shall be attached to the Batch document (BMR or BPR) as per the template attached as Annexure-1.
    • Where the yield is fixed, any out of limit obtained shall be investigated for possible reasons.
    • The investigation shall be done on an unplanned deviation format (Refer SOP for Deviation).
    • The head of the Department of Production shall provide a reason for the out of limit yield with corrective and preventive actions.

5.0   ABBREVIATION(S) :

    • BMR: Batch Manufacturing Record
    • BPR: Batch Packaging Record

Annexure – I:  Yield certificate (template)

The yield of the  …………………………………………………………………. (Product Name) has been fixed after completion of 10 consecutive batches  (      ) / after completion of Product Quality Review (  ) (tick the appropriate)

The fixed limits are as below

Sr. No

Stage Previous Limit

Revised Limit

1.
2.
3.      

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pharmabeginers

Janki Singh is experienced in Pharmaceuticals, author and founder of Pharma Beginners, an ultimate pharmaceutical blogging platform. Email: [email protected]

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